@article{a3234b75b48e4ed7b5761ec5d0d84cf7,
title = "Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2",
abstract = "A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10-8) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log 10 odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.",
author = "Wright, {Fred A.} and Strug, {Lisa J.} and Doshi, {Vishal K.} and Commander, {Clayton W.} and Blackman, {Scott M.} and Lei Sun and Yves Berthiaume and David Cutler and Andreea Cojocaru and Collaco, {J. Michael} and Mary Corey and Ruslan Dorfman and Katrina Goddard and Deanna Green and Kent, {Jack W.} and Lange, {Ethan M.} and Seunggeun Lee and Weili Li and Jingchun Luo and Mayhew, {Gregory M.} and Naughton, {Kathleen M.} and Pace, {Rhonda G.} and Peter Par{\'e} and Rommens, {Johanna M.} and Andrew Sandford and Stonebraker, {Jaclyn R.} and Wei Sun and Chelsea Taylor and Vanscoy, {Lori L.} and Fei Zou and John Blangero and Julian Zielenski and O'Neal, {Wanda K.} and Drumm, {Mitchell L.} and Durie, {Peter R.} and Knowles, {Michael R.} and Cutting, {Garry R.}",
note = "Funding Information: This work was supported in part by grants from the US National Heart, Lung and Blood Institute R01HL068927, R01HL068890, R01HL095396, the US National Institute of Diabetes and Digestive and Kidney Diseases R01DK066368, K23DK083551, P30DK027651, the US National Institute of Mental Health SOLAR-MH059490 and the US National Human Genome Research Institute HG-0004314; US Cystic Fibrosis Foundation grants CUTTIN00A0, CUTTIN06P0, COLLAC07A0, RDP-R025-CR07, KNOWLE00A0, RDP-R026-CR07, DRUMM0A00 and contract GENOMEQUEBEC07DDS0; Flight Attendant Medical Research Institute grant FAMRI2006; Lawson Wilkins Pediatric Endocrine Society grant LWPES Clinical Scholar Award; The Canadian Cystic Fibrosis Foundation; Genome Canada through the Ontario Genomics Institute as per research agreement 2004-OGI-3-05; Ontario Research Fund, Research Excellence Program; Lloyd Carr-Harris Foundation; and the Joint Fellowship of Canadian Institutes of Health Research and Ontario Women{\textquoteright}s Health Council. Funds for genome-wide genotyping were generously provided by the US Cystic Fibrosis Foundation (CFF).",
year = "2011",
month = jun,
doi = "10.1038/ng.838",
language = "English (US)",
volume = "43",
pages = "539--546",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "6",
}